A Phase I Study in Healthy Volunteers and Parkinson's Disease (PD) Patients.

NCT07630545 | Recruiting Phase 1 DMC

• 2 other identifiers: MTX325-1012024-517310-15-01
• Study Type: interventional
• Target: 106
• Locations: 4 countries
• Sites: 18

Brief Summary

The goal of this trial is to learn if MTX325 can be developed as a potential disease-modifying treatment for Parkinson's Disease. Parts 1-4 complete, Part 5 (multiple doses in patients with Parkinson's Disease) in progress.

Conditions

Parkinson's Disease (PD); Mild to Moderate Parkinson's Disease; Early Stage Parkinson's Disease

Keywords

Parkinson's disease; MDS-UPDRS; CSF; Plasma; Biomarkers; Mild; Moderate; Hoehn and Yahr scale

Outcome Measures

Primary Outcomes (3)

• Safety and Tolerability

  To assess the safety and tolerability of single ascending doses of MTX325, when administered to participants. Adverse Events will be collected. The following vital signs will be measured to form the safety and tolerability outcome- blood pressure, heart rate, oral body temperature, respiratory rate. Laboratory Safety analyses will include biochemistry, haematology, and urinalysis. 12-lead ECG will be performed to collect heart rate, RR interval, PR interval, QRS width, QT interval, and QTcF interval. All participants who receive at least 1 dose of IMP will be included in the safety analysis.

  up to 28 days post dose

• Brain Biodistribution

  To investigate the brain biodistribution in MTX325. This part of the protocol is intended to ascertain the biodistribution of MTX325 in the brain. Radiolabelled MTX325 will be injected and PET images taken to determine the whole brain and regions of interest distribution volume. MRI images will be performed to be able to co-register regions of interest.

  MRI performed during screening period and PET performed on Day 1

• Safety and Tolerability

  To evaluate the safety and tolerability of MTX325 in untreated participants with mild to moderate idiopathic PD. Adverse Events will be collected. The following vital signs will be measured to form the safety and tolerability outcome - blood pressure, heart rate, oral body temperature, respiratory rate. Laboratory Safety analyses will include biochemistry, haematology, and urinalysis. 12-lead ECG will be performed to collect heart rate, RR interval, PR interval, QRS width, QT interval, and QTcF interval. All participants who receive at least 1 dose of IMP will be included in the safety analysis.

  up to 28 days post dose

Study Arms (4)

Parts 1 - 4

ACTIVE COMPARATOR

MTX325 Active Oral Capsules - 1.5mg - 100mg These 4 parts are SAD, MAD, Elderly and PET biodistribution.

Drug: MTX325

Parts 1 - 3, and 5

PLACEBO COMPARATOR

MTX325 Placebo Capsules - 50mg. Parts 1-3 are SAD, MAD and Elderly cohorts. Matched strength placebo capsules in Part 5 (PD participants)

Other: Placebo

Part 4

ACTIVE COMPARATOR

MTX325 Capsules - 20mg. Radiolabelled MTX325 solution for injection. This is a healthy volunteer PET study. Not placebo controlled.

Drug: MTX325

Part 5

ACTIVE COMPARATOR

MTX325 - 20 mg Capsules

Drug: MTX325

Interventions

MTX325 DRUG

MTX325

Part 4; Part 5; Parts 1 - 4

Placebo OTHER

Placebo

Parts 1 - 3, and 5

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female participants aged ≥ 40 to ≤ 75 years.
• Male or female participants. Female participants of childbearing potential must be willing to use highly effective forms of contraception (refer to Section 9.7.1 for details on highly effective methods of contraception and definitions of women of childbearing potential and of fertile men):
• Body mass index (BMI) between 18 and 34.0 kg/m2, inclusive.
• If being treated with selective serotonin reuptake inhibitors (SSRIs) for anxiety/ depression, must be on a stable dose for 60 days prior to Day -1 and must remain on that dose for the remainder of the study.
• Must have had other causes of Parkinsonism excluded
• No clinically significant history of previous allergy/ sensitivity to MTX325 or any of the excipients contained within the IMP.
• Participant with a negative urinary drugs of abuse (DOA) screen (excluding alcohol).
• Participant with negative human immunodeficiency virus (HIV), hepatitis B surface antigen \[HbsAg\]) and hepatitis C virus antibody (HCV Ab) test results at Screening.
• No history of torsade de pointes or long QT syndrome and no heart failure, hypokalaemia, or any other additional cardiac risk factors if judged clinically significant in the opinion of the Investigator.
• No clinically significant abnormalities in vital signs during the screening period.
• Able to perform all protocol assessments and comply with the study visit schedule.
• Able and willing to provide informed consent.
• Clinically established PD as per MDS Criteria\[
• Absence of dementia as shown by a baseline Montreal Cognitive Assessment (MoCA®)

You may not qualify if:

• A clinically significant history of gastrointestinal disorders or any significant medical conditions that would be likely to influence IMP absorption, or evidence of clinically significant central nervous system, respiratory, cardiovascular or metabolic dysfunction or other significant medical conditions with potential to impact participant safety or hinder interpretation of study results.
• Clinically significant neurologic disorder other than PD, including history of stroke within 12 months of Screening, seizure within 5 years of Screening, or head trauma with loss of consciousness within 6 months of Screening.
• Those with known PD risk genes (per medical history).
• Reside in a nursing home or assisted care facility.
• No more than 2 PD related freezing episodes or falls in the past 6 months.
• Any condition that may predispose participant to complications or technical difficulty with lumbar puncture, in the opinion of the Investigator.
• Participants who have conditions that would preclude a lumbar puncture (LP), such as a local infection at the site
• Participant who has a history of clinically significant hypersensitivity to local anaesthesia, or its derivatives used during CSF collection or to any medication used to prepare the area of LP.
• Reports having experienced suicidal ideation (Type 4 on 5 on the Columbia-Suicide Severity Rating Scale \[C-SSRS©\]
• Participants should not be in receipt of any known MATE2k substrates
• Plan to receive or administration of rotigotine, catechol-o-methyltransferase (COMT) inhibitors (e.g., entacapone, tolcapone or opicapone), neuroleptics, venlafaxine, NMN, nicotinamide riboside or non-selective Monoamine oxidase \[MAO\] inhibitors within 7 days or 5 half-lives (whichever is longer) prior to first dose and during the study conduct.
• Clinically significant abnormal test results for serum biochemistry, haematology, coagulation and/or urine analyses as determined within 45 days before first dose of IMP.
• A clinically significant history of gastrointestinal disorder likely to influence IMP absorption.
• Participant has any condition that, in the opinion of the investigator, is clinically significant and may put the participant at greater safety risk, influence response to study product, or interfere with study assessment.
• Inability to communicate well with the Investigators.

Sponsors & Collaborators

• Mission Therapeutics: lead
• Parkinson's UK: collaborator
• Michael J. Fox Foundation for Parkinson's Research: collaborator

Study Sites (18)

The Royal Adelaide Hospital

Adelaide, Australia

NOT YET RECRUITING

Doherty Clinical Trials

Melbourne, Australia

RECRUITING

Monash Health, Kingston Centre

Melbourne, Australia

NOT YET RECRUITING

Centre Hospitalier Universitaire de Lille, Institut Cœur Poumon

Lille, France

RECRUITING

Hôpital Henri-Mondor (Créteil, AP-HP), Paris

Paris, France

NOT YET RECRUITING

Pitie-Salpetriere Hospital, Paris

Paris, France

NOT YET RECRUITING

Centre Hospitalier Universitaire (CHU) de Toulouse, Toulouse

Toulouse, France

NOT YET RECRUITING

Technische Universitaet Dresden, Dresden

Dresden, Germany

NOT YET RECRUITING

Cambridge Biomedical Research Centre, Cambridge

Cambridge, United Kingdom

NOT YET RECRUITING

Neuroclnx, Glasgow

Glasgow, United Kingdom

NOT YET RECRUITING

Royal Liverpool University Hospital

Liverpool, United Kingdom

RECRUITING

Parexel

London, United Kingdom

COMPLETED

Perceptive

London, United Kingdom

COMPLETED

Simbec-Orion

Merthyr Tydfil, United Kingdom

COMPLETED

Freeman Hospital, Newcastle Upon Tyne

Newcastle, United Kingdom

RECRUITING

University Hospitals Plymouth NHS Trust, Derriford Hospital

Plymouth, United Kingdom

RECRUITING

Salford Hospital (Manchester)

Salford, United Kingdom

NOT YET RECRUITING

Southampton General Hospital, Southampton

Southampton, United Kingdom

RECRUITING

MeSH Terms

Conditions

Parkinson Disease; Lymphoma, Follicular

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

Sarah J Fritchley, PhD

CONTACT

sfritchley@missiontherapeutics.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: Participants will receive either MTX325 or placebo

Study Record Dates

• First Submitted: May 6, 2026
• First Posted: June 5, 2026
• Study Start: November 30, 2023
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 27, 2027
• Last Updated: July 29, 2026

Record last verified: 2026-07

Locations

GB (10); FR (4); AU (3); DE (1)